Localized cell stimulation by nitric oxide using a photoactive porous coordination polymer platform

Abstract

Functional cellular substrates for localized cell stimulation by small molecules provide an opportunity to control and monitor cell signalling networks chemically in time and space. However, despite improvements in the controlled delivery of bioactive compounds, the precise localization of gaseous biomolecules at the single-cell level remains challenging. Here we target nitric oxide, a crucial signalling molecule with site-specific and concentration-dependent activities, and we report a synthetic strategy for developing spatiotemporally controllable nitric oxide-releasing platforms based on photoactive porous coordination polymers. By organizing molecules with poor reactivity into polymer structures, we observe increased photoreactivity and adjustable release using light irradiation. We embed photoactive polymer crystals in a biocompatible matrix and achieve precisely controlled nitric oxide delivery at the cellular level via localized two-photon laser activation. The biological relevance of the exogenous nitric oxide produced by this strategy is evidenced by an intracellular change in calcium concentration, mediated by nitric oxide-responsive plasma membrane channel proteins.

Light responsive metal–organic frameworks as controllable CO-releasing cell culture substrates

“…A second spin coating of a gas permeable and biocompatible polymer matrix (PDMS, polydimethylsiloxane) was embedded the CORF-1_small_79 crystals. As we previously confirmed for the similar NO-release framework system, 24 this configuration allowed the adhesion and culture of living cells on the top of the PDMS layer and gave no chance for embedded crystals to be dissolved into cell culture media, and thus promised almost no cytotoxicity. Before light irradiation experiments, the HeLa cells were treated with a turn-on fluorescent probe (COP-1) suitable for the intracellular detection of CO. 36 The illumination of the MOF-based substrate by white light resulted in an unambiguous increase in the fluorescence of the HeLa cells treated with the COP-1 probe, as observed by confocal laser scanning microscopy (Fig.…”

“…Indeed, we have recently demonstrated the advantage of photoactive MOFs for the controlled delivery of biologically active nitric oxide (NO) molecules at the cellular level. 24,25 Although there has been only one example of CO-releasing MOF, 26 in which CO gas is first adsorbed onto open metal sites and then steadily released through ligand exchange reaction with water in physiological media, to the best of our knowledge, highly controllable release of CO from MOFs is yet to be achieved.…”

Application of metal and metal oxide nanoparticles@MOFs

“…16d); however, controlled release of the drug via an alternating magnetic field was not demonstrated. We note that HKUST-1 is known to be water sensitive [197], hence the spontaneous release of NIM may be attributed to the decomposition of HKUST-1. [196].…”

Emerging applications of metal–organic frameworks

“…Reference source not found.). 46 These frameworks did not release any NO molecules under ambient conditions, but did release NO under UV light irradiation. NO release duration and kinetics could be controlled by the irradiation time and intensity, respectively.…”